Effect of HIV status on Th17/IL-17 immune function in subjects undergoing tuberculosis treatment in Kenya

Abstract Mycobacterium tuberculosis and HIV remain top global public health concern. Complexities associated with Mtb/HIV coinfections, including in those virally suppressed with anti-retroviral therapy (ART), present significant challenges to efforts to reduce both infections. The pattern of cytokines produced by T helper (Th) lymphocytes plays a central role in susceptibility, relapse and reinfection to TB. To understand how HIV and ART status affects recovery of Th cell effector function, we conducted a prospective study of HIV+ or HIV- subjects from Nairobi, Kenya. Blood samples were taken at start of TB treatment and 5 months after. Cytokine bead array was used to assess human Th cell-derived cytokines isolated from plasma from Nil, TB1 and Mitogen QuantiFERON tubes, including; IL-4, IL-9, IL-10, IL-17A, IL-17F, IL-22, IFN-γ and TNF-α. Intracellular cytokine staining (ICS) of cryopreserved peripheral blood mononuclear cells was also performed to determine changes in baseline numbers of Th1, Th2, Th17, Th22, IL-10+ Th cells, as well as HIV+ Th cells, across treatment groups. Results show reduced plasma IL-9, IFNg and IL-22 activation by mitogen in TB+HIV+ subjects that is independent of ART status, while IL-17A is moderately reduced in TB+HIV+ART- subjects. Cytokine recall to TB1 antigen was observed to be similar across all treatment groups, with the exception that a moderate reduction of IFNg and IL-17A was observed in the TB-HIV+ group. In subjects compliant for ART, ISC analysis revealed greater numbers of HIV+ cells in TB+HIV+, compared to TB-HIV+, groups. These preliminary results identify defects in effector cytokines produced by Th cells that may persist after ART and contribute to poorer TB treatment outcomes in subjects with HIV. Supported by NIH, NIAID, 1R01AI147948